Huntington’s Disease Patients May Benefit From Treatment for Sleep Dysfunction

A review published in the journal Nature and Science of Sleep explores the links between sleep disturbance and neurodegeneration in diseases such as Huntington’s disease (HD). The authors state that sleep difficulties might not only be a symptom of the underlying neurodegeneration but also a contributing factor driving the disease.

Up to 90 percent of HD patients suffer from sleep disturbance, including difficulty initiating and maintaining sleep, reduced sleep efficiency and less total sleep time. Studies have shown that as the disease progresses, circadian rhythm disturbances become progressively worse. Research indicates that in the case of HD, hypnotic drugs can improve sleep-wake patterns and, as a consequence, cognition.

The review notes that there is increasing evidence that sleep disturbances observed in patients with HD and other neurodegenerative diseases have a neuroanatomical basis. Reduced numbers of neurons in the suprachiasmatic nucleus – a brain region that is considered the circadian pacemaker in mammals – are linked to the amplitude of sleep-wake activity.

Sleep disturbance is also associated with altered secretion of melatonin, an antioxidant that protects cells from oxidative stress. Researchers have found that in addition to mirroring sleep disturbance, reduced melatonin signaling may actually speed up the progression of disease. And, melatonin can block the assembly and toxicity of α-synuclein – a protein which aggregates in the brains of Parkinson’s disease patients and might also contribute to HD.

Another factor of interest is the neuropeptide orexin, which maintains wakefulness and stabilizes sleep-wake transitions. Studies have shown that the neuropeptide might play a role in sleep fragmentation and excessive sleepiness often observed in diseases such as HD. Both patients with HD and mouse models of the disease have reduced numbers of orexin-positive neurons in the hypothalamus region of the brain. These changes are often mirrored by orexin levels in the cerebrospinal fluid of patients, suggesting that a substantial neuron loss is needed before changes can be seen in cerebrospinal fluid samples.

Experimental studies also suggest that orexin can be neuroprotective in a cell model of Parkinson’s disease, indicating that a loss of orexin-producing cells might play a role in sleep-wake disturbances, but also that cell loss might contribute to disease progression.

The presence of co-morbid sleep disorders is yet another factor that might influence neurodegeneration. Obstructive sleep apnea, resulting in occasional low oxygen levels and sleep fragmentation impair memory and have been associated with a reduced volume of memory-related brain areas. Yet other studies show that neurocognitive performance deficits might be lined to sleep apnea-induced hypoxia.

There is plenty of evidence that sleep disruption can be an early symptom of neurodegenerative disease. Sleep disturbance often precedes clinically evident symptoms of neurodegeneration. This opens up the possibility that sleep disruption plays a role in the development and progression of diseases such as HD.

The authors state that more research is needed to clarify whether sleep disturbances are causing the neurodegenerative process or if they are merely a symptom of disease. They say that since sleep is a factor that lends itself to pharmaceutical modification, the idea to develop and test neuroprotective and disease-modifying strategies is an exciting concept. Regardless of underlying mechanisms, attempts to treat the disturbed sleep-wake patterns may be beneficial for patients.

Magdalena is a writer with a passion for bridging the gap between the people performing research, and those who want or need to understand it. She writes about medical science and drug discovery. She holds an MS in Pharmaceutical Bioscience and a PhD — spanning the fields of psychiatry, immunology, and neuropharmacology — from Karolinska Institutet in Sweden.

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